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ORIGINAL RESEARCH article

Front. Genet.
Sec. Applied Genetic Epidemiology
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1421824

Causal associations between severe COVID-19 and diseases of seven organs: A proteome-wide Mendelian randomization study

Provisionally accepted
Yunhan Shen Yunhan Shen 1Yi Zhang Yi Zhang 2Ye-Yang Xu Ye-Yang Xu 3Xinyi Li Xinyi Li 1Jiachen Wu Jiachen Wu 1Hao Pei Hao Pei 4Linyan Wang Linyan Wang 5Tiansheng Zhu Tiansheng Zhu 1*
  • 1 Zhejiang Agriculture and Forestry University, Hangzhou, China
  • 2 First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
  • 3 Songyang County People's Hospital, Lishui, China
  • 4 MobiDrop(Zhejiang) Co., Ltd, Tongxiang, China
  • 5 Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    The coronavirus disease 2019 pandemic poses an enormous threat to public health worldwide. Many retrospective studies and case reports to date have shown associations between severe COVID-19 and diseases of multi-organs. However, the research on the causal mechanisms behind this phenomenon is neither extensive nor comprehensive. We conducted a proteome-wide Mendelian randomization (MR) study using summary statistics from a genome-wide association study (GWAS) of severe COVID-19 and diseases related to seven organs: lung, spleen, liver, heart, kidney, testis, and thyroid, based on the European ancestry. The primary analytical method used is the radial inverse variance-weighted (radial IVW) method, supplemented with the inverse varianceweighted (IVW), weighted-median (WM), MR-Egger methods. Our findings have confirmed the association between severe COVID-19 and multiple organ-related diseases, such as Hypothyroidism, strict autoimmune (HTCBSA), Thyroid disorders (TD), and Graves' disease (GD). And we have also identified certain proteins that are associated with organ-related diseases, such as Superoxide Dismutase 2 (SOD2) and TEK Receptor Tyrosine Kinase (TEK), which are also considered potential drug targets. Phenotype scanning and sensitivity analyses were implemented to consolidate the results for Mendelian randomization. This study provides a compelling foundation for investigating COVID-19 caused diseases in future studies.

    Keywords: Severe COVID-19, Causal effect, Mendelian Randomization (MR), Organ-related diseases, Proteome

    Received: 23 Apr 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Shen, Zhang, Xu, Li, Wu, Pei, Wang and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tiansheng Zhu, Zhejiang Agriculture and Forestry University, Hangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.